Beggs Laboratory | Information for Patients and Families

Thank you for your interest in our research! Boston Children's Hospital is well known for its combination of first rate clinical care and for its outstanding research. Our laboratory is part of the Division of Genetics in the Department of Medicine at Boston Children's Hospital. We have been committed to the study of neuromuscular disease since the early 1990's. Our group includes a team of scientists and doctors whose goal is determining which genes and proteins are involved in neuromuscular disease.

We are also affiliated with the Department of Pediatrics of Harvard Medical School. As a Harvard academic affiliate, our lab has been the training site for a number of researchers that have made important contributions to the genetics field. We are proud to say that many of our alumni are still working on neuromuscular disease.

The results derived from our research have shed light into some of the most difficult questions about the genetics of the congenital myopathies. Our progress has been made possible in part thanks to the generosity of many families around the world who have participated in our research. Families enroll in our studies because they want to contribute to research, hoping that their participation may eventually benefit all individuals with neuromuscular disease. Our goals are to help all patients and their families by improving diagnostic methods and treatments for these disorders.

By clicking on the links on the left, you will be taken to pages with information about muscle disease and function, resources, our research, ways to help, and answers to frequently asked questions.

The Myopathies

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OVERVIEW

The "myopathies" is the name given to a group of neuromuscular disorders that affect skeletal muscle, causing generalized muscular weakness among other symptoms. Literally, the word myopathy means "disease of the muscle" (myo=muscle; Gr. pathos=disease). Other types of myopathies are the inflammatory myopathies, the channelopathies, the metabolic myopathies, the mitochondrial myopathies, the dystrophic myopathies, and the non-dystrophic myopathies. Although all these myopathies affect skeletal muscle, the mechanisms that cause disease are different in each type.

In the Beggs laboratory, we focus on a group of non-dystrophic myopathies, known as the congenital myopathies because they are often present from birth. Individuals who have a congenital myopathy often have slowly or non-progressive muscular disorders characterized by hypotonia (low muscle tone) and muscle weakness. Sometimes, there are multiple affected family members within a family. Therefore, it is thought that the congenital myopathies are genetic. Genetic conditions are those that arise from gene changes. We are trying to identify and study the genes and proteins involved in the causes of:

congenital fiber type disproportion

minicore/multicore myopathy

myotubular myopathy

nemaline myopathy

non-specific congenital myopathies (for which an established diagnosis has not been made)

DIAGNOSIS

The congenital myopathies are similar in nature as they all cause low muscle tone and weakness. However, when muscle tissue samples from patients with different types of congenital myopathies are examined under the microscope, more differences can be observed. Thus, the diagnosis is usually made by the appearance of a muscle sample under the microscope. These studies, also known as "histochemical analyses", make it possible to distinguish between each type of congenital myopathy. While histochemical studies are very useful in establishing a diagnosis, they usually do not tell the actual genetic change that underlies the disorder.

VARIABILITY

Although the congenital myopathies are often clinically similar, there is a wide spectrum of variability within each. In other words, not everybody will have the same medical issues. Some patients with certain types may not survive past the first few years of life, while others may walk independently through adulthood and have families of their own. If you are interested in obtaining clinical information about any of the congenital myopathies, you may want to contact Dr. Susan Iannaccone, a pediatric neurologist who has been involved in the care of many patients with these disorders. In addition, the Muscular Dystrophy Association (MDA) provides excellent online brochures on neuromuscular disease as well as contact information of MDA clinic sites across the United States.

GENETICS

As mentioned earlier, most congenital myopathies are thought to have a genetic cause. This means that these disorders are often caused by alterations in genes that play a role in muscle function and/or development. A gene is a portion of DNA that harbors a specific instruction for the body. We inherit our genes from our parents and we pass them on to our children.

It is an interesting fact that frequently, the congenital myopathies occur in families where there is no previous history of neuromuscular disorders. In these instances, we say the disorder is "sporadic". Sporadic conditions happen when a genetic change suddenly appears in an individual, causing disease. Although genetic changes can arise sporadically, once the change appears in an individual, there is a possibility that the individual can pass the alteration to his/her children. One of our goals is to detect and understand how these alterations arise and how they are inherited.

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Muscle Anatomy and Genetics

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This section contains information about different muscle types, with emphasis on skeletal muscle. We will also go over the structure and function of muscle tissue. Finally, as muscle composition is determined by our genes, a brief introduction to certain genetics concepts will be presented.

Muscle tissue is specialized for contraction and movement and it is found in two main forms: smooth and striated. Smooth muscle is present in those body systems that are under involuntary control. The digestive tract and the respiratory passages, among others, are made primarily of smooth muscle. Striated muscle is present in the heart and in the muscles that control our movements and breathing. Striated muscle owes its name to the interesting array of bands that becomes visible at the microscopic level. The origin and importance of these bands will be discussed further into this section. Striated muscle can be divided into two sub-types: cardiac muscle and skeletal muscle. Cardiac muscle, as the word implies, makes up the walls of the heart. Skeletal muscle is connected with the nerves, and because movement of these muscles can be consciously controlled, it is known as voluntary muscle. Most skeletal muscle is attached to our skeleton (hence its name) by a special form of tissue called tendons. In the Beggs Lab, we focus on the study of conditions that are caused by primary defects of skeletal muscle structure and function. These disorders are also known as myopathies. For a schematic representation of the different types of muscle tissue, see Figure 1 below.

SKELETAL MUSCLE STRUCTURE

Like any type of muscle, skeletal muscle is made of specialized cells called myofibers. Myofibers contain bundles of even smaller, thread-like structures called myofibrils. The myofibrils make up the machinery that allows movement and the use of force in daily activities. They contain many different specialized proteins that assemble together in a highly organized manner to form "thick filaments" and "thin filaments". The interaction between the proteins that form the thick and the thin filaments is what generates muscle contraction.

In summary, skeletal muscle is made of fibers, fibers are made of myofibrils, and myofibrils are made of proteins, which in turn form the thick filaments and the thin filaments. Figure 2 summarizes the elaborate composition of muscle tissue.

As stated at the beginning, when striated muscle is examined under a microscope, a distinct repeating pattern of bands can be observed. Each repeating unit (also known as the sarcomere), formed by the Z, I, A, H, and the M bands, is the product of the interaction between the proteins that form the thick filaments and the thin filaments. One of the goals of our lab is to characterize the proteins that form the sarcomere (sarcomeric proteins), hoping to identify new genes that are associated with disorders of muscle contraction.

Research has already unraveled many of the sarcomeric proteins that are responsible for skeletal muscle contraction. The names of some of these proteins are actin, myosin, troponin, tropomyosin, andnebulin. When skeletal muscle fibers receive a nerve impulse, these proteins (and others yet to be identified) are believed to change their shape and position. The thick filaments pull on and slide along the thin filaments, causing the sarcomere to shorten and the muscle to contract.

GENETICS

Just like the rest of the proteins in the body, instructions to make the sarcomeric proteins are encoded by different genes in the DNA. The DNA is actually a long string formed by four chemicals, namely, Adenine, Guanine, Cytosine, and Thymine (A, G, C, and T). The order in which these chemicals are found is what determines the genetic code, or sequence. A change in this order (i.e. mutation) results in a change of the encoded protein.

Proteins play many roles in the body. For example, they give the cues for development, determine eye color, and help in food digestion, among others. Proteins are essential for body function and therefore, certain protein alterations can cause disease. In particular, alterations in any of the sarcomeric muscle proteins can potentially cause muscle disease. For example, alterations in actin are known to cause nemaline myopathy, a disease of skeletal muscle that causes low muscle tone, muscle weakness and respiratory difficulties, among others. Protein alterations are caused by gene changes (mutations).

At this point, it is worth mentioning that not all genetic changes have an impact on our health. Although the vast majority of the DNA is very similar among different people, some parts of the DNA may vary. All human beings are different. People have different skin color, hair, and eye color. The reason for these differences is that everybody's DNA is different. Most of the time, the DNA changes that produce different skin or eye colors do not have an impact on our health. In addition, many DNA changes are "silent", having no known effects on our development.

"Silent" DNA changes do not cause disease or differences between individuals. When a new mutation is found in an individual, it is important to confirm whether the DNA change is disease causing or not. In the Beggs lab, we do that by comparing samples from affected to non-affected family members, as well as to samples from members of the general population. If a mutation is present in both affected and non-affected family members, then we are likely to conclude that this mutation does not cause disease.

A genetic change that interferes with somebody's health must be significant enough so that the function of the protein encoded by the gene becomes altered. The outcome of a particular gene alteration is also dependent on how essential to the body is the protein made by that gene. Certain mutations in the genes encoding actin, nebulin, troponin, and tropomyosin cause nemaline myopathy, a disease associated with muscle weakness and respiratory problems. Similarly, mutations in the gene for myotubularin 1 cause X-linked myotubular myopathy, a severe condition associated with muscle weakness, skeletal problems, and fatigability. Specific genetic cause(s) for multiminicore disease, congenital fiber-type disproportion (CFTD), as well as certain non-specific myopathies are the subject of current research.

Identification of mutations may lead to better understanding of basic muscle biology, will allow for the development of improved diagnostic tests, and will hopefully lead to insights into therapies. This is why the Beggs lab is actively looking for congenital myopathy-causing genetic changes.

Diseases

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The congenital myopathies are a sub-group of neuromuscular conditions that affect skeletal muscle. This group of disorders are often, but not always, present at birth. Hence the name congenital myopathies.

The congenital myopathies are similar in nature, often causing muscle weakness and low muscle tone of varying degrees. Diagnosis is usually made from a muscle biopsy. In these, specific myopathic findings such as nemaline rods or central cores can be observed. These findings allow determination of the type of congenital myopathy that is present.The congenital myopathies are a sub-group of neuromuscular conditions that affect skeletal muscle. This group of disorders are often, but not always, present at birth. Hence the name congenital myopathies.

In the Beggs Laboratory, we are interested in determining the genes that are involved in the cause of these congenital myopathies. By clicking on the links above, you will be taken to general information as well as a description of our research studies on each disease.

Congenital Fiber Type Disproportion

Congenital myopathy with fiber type disproportion (CFTD) is one of the rare forms of neuromuscular disease that are present at birth. The most common medical problems associated with CFTD are scattered muscular weakness, low muscle tone, and bone deformities. Other medical issues may include absent or low tendon reflexes and life threatening respiratory problems. Diagnosis is made by a muscle biopsy. Muscle biopsies of patients with CFTD show a disproportion in the size of type I and type II fibers. In muscle biopsies with CFTD, type I fibers are smaller than type II fibers. Other associated muscle biopsy findings are fiber I predominance and absence of type IIB fibers.

Genetics

The specific genetic changes responsible for causing CFTD are not known. This condition often occurs in patients who have no prior family history of the disorder. In other occasions, there may be several affected family members. When more than one family member is diagnosed with CFTD, the condition is probably inherited. In these cases, CFTD can be inherited in an autosomal dominant or an autosomal recessive mode of inheritance.
Since the genetics of CFTD have not been unraveled yet, our laboratory is interested in studying DNA and muscle biopsy samples of these patients since it would provide insight into the genetic cause of their muscular condition. Identification of the genes involved in CFTD could have direct clinical benefit to patients and their families by allowing for specific diagnostic testing such as carrier detection and prenatal diagnosis for those who wish. Furthermore, understanding the genetic cause(s) of congenital myopathies will increase our understanding of muscle biology and provide insights into future development of specific treatments and therapies.

Research

One of the goals of the research done at the Beggs laboratory is to determine which genes and proteins are involved in the cause of CFTD. We hope that what we learn will be useful for improving diagnosis and treatment of this condition. If you are the parent of a child with a congenital myopathy, if you yourself are affected, or if you are the healthcare provider of someone with CFTD, you may be able to help us better understand CFTD and to determine the genetic changes associated with the condition.

Multiminicore Disease - MmD

Multiminicore disease consists of a spectrum of congenital neuromuscular conditions with clinical similarities such as non-progressive weakness and the presence of structural muscular changes in muscle biopsies. Muscle biopsies of patients with multiminicore disease often show variation in fiber size and occasional fiber splitting. Another muscle biopsy finding is the marked predominance of type I fibers. This condition is associated with muscular weakness and gait problems. Although multiminicore disease is usually non-progressive, a few patients experience muscle deterioration. Other medical problems may include heart disease, respiratory problems, and increased risk for malignant high blood temperature with anesthesia.
Our laboratory is interested in studying DNA and muscle biopsy samples from patients with multiminicore disease since it would provide insight into the genetic cause of their muscular condition. Identification of the genes involved in this disorder could have direct clinical benefit to patients and their families by allowing for specific diagnostic testing such as carrier detection and prenatal diagnosis for those who wish. Furthermore, understanding the genetic cause (s) of congenital myopathies will increase our understanding of muscle biology and provide insights into future development of specific treatments and therapies.

Genetics

Multiminicore disease appears to be caused by alterations in certain genes that are involved in muscle function and/or development. Multiminicore disease most often occurs in families with no previous history of neuromuscular disease. To date mutations have been found in two genes, Selenoprotein N1 (SEPN1) and Ryanodine receptor 1 (RYR1), which together account for about half the cases. A third of all multiminicore disease cases are due to mutations of the SEPN1 gene. In addition, SEPN1 mutations cause a phenotypically distinct condition called Rigid Spine Muscular Dystrophy (RSMD). RSMD and multiminicore disease due to SEPN1 mutations are also called SEPN-related myopathy. The function of selenoprotein N is yet to be determined, while ryanodine receptor regulates calcium channels. Testing for these mutations is available only on a research basis. For more information, contact us.

Research

One of the goals of the research done at the Beggs laboratory is to determine which genes and proteins are involved in the cause of multiminicore disease. We hope that what we learn will be useful for improving diagnosis and treatment of these conditions. If you are the parent of a child with this condition, if you yourself are affected, or if you are the healthcare provider of a person with multiminicore disease, you may be able to help us expand our knowledge in this condition and perhaps develop better tests, treatments and therapies.

Myotubular and Centronuclear Myopathy - CNM

Myotubular myopathy is a neuromuscular condition that is associated with muscle weakness, skeletal problems, gait problems and fatigability among other medical problems. Although there are many clinical findings associated with this condition, the presentation of the disease varies from individual to individual. For instance, myotubular myopathy can be present in its life-threatening, neonatal form, it can be present in its less severe, intermediate form, or it can appear later in life in its slowly progressive form. Our laboratory is interested in studying DNA and muscle samples of these patients since it would provide insight into the genetic cause of their muscular condition.
Identification of these genes could have direct clinical benefit to patients and their families by allowing for specific diagnostic testing such as carrier detection and prenatal diagnosis for those who wish. Furthermore, understanding the genetic cause (s) of myotubular myopathy will increase our understanding of muscle biology and provide insights into future development of specific treatments and therapies.

Genetics

Once a myotubular myopathy-causing genetic alteration appears in an individual, it can be passed on in three different patterns of inheritance: autosomal dominant, autosomal recessive, and X-linked. The autosomal dominant form of myotubular myopathy is usually associated with slow progression of muscle weakness. When myotubular myopathy is inherited in an autosomal recessive fashion, onset is not neonatal, but usually earlier than that of the autosomal dominant form. In addition, the degree of severity of this form is often intermediate. The X-linked form of myotubular myopathy is usually associated with neonatal onset and severe presentation.
While currently there is no clinical diagnostic genetic testing for the autosomal dominant and the autosomal recessive forms of myotubular myopathy, the University of Chicago offers clinical diagnostic genetic testing for the X-linked form of myotubular myopathy. Genetic testing at the University of Chicago consists of screening the gene that makes an X-linked muscle-specific protein called myotubularin 1.

Research

Since there are patients with myotubular myopathy with no detectable gene change, it is the purpose of our study to determine what other genes are responsible for the cause of myotubular myopathy, how they can arise and how they are inherited. Our group of scientists and doctors is trying to understand the changes that occur in the muscle of patients with myotubular myopathy, with the hope that this will lead to improved treatment for this condition. In order to carry out our research, we need the help of families. If you are the parent of a child with myotubular myopathy, if you yourself are affected, or if you are a healthcare provider of a patient with myotubular myopathy, you may be able to help us to develop better therapies and treatments for this disorder.

Nemaline Myopathy

Nemaline myopathy (NM) is a rare neuromuscular disease that is associated with a broad range of special medical needs, such as weakness of the respiratory muscles and those in the face, arms, legs and the trunk as well as low muscle tone. Diagnosis is based on the presence of rod-like structures known as "nemaline bodies" in a patient's muscle biopsy.
The clinical presentation of nemaline myopathy can be quite variable. Some patients have a few findings while others may have numerous issues that require constant medical attention. Most patients have symptoms at birth or start developing symptoms during the first year of life. When nemaline myopathy is present at birth, the disease outcome is usually more severe. Patients with this form of NM show distinct muscle weakness and low muscle tone. These patients tend to have serious, life-threatening breathing problems due to respiratory muscle weakness. There are also later-onset forms of nemaline myopathy, with milder symptoms appearing in childhood or adulthood.
For more information, read the Review Article on NM.
Our laboratory is interested in studying DNA and muscle tissue samples of these individuals since it would provide insight into the genetic cause of their muscular condition. Identification of these genes could have direct clinical benefit to patients and their families by allowing for specific diagnostic testing such as carrier detection and prenatal diagnosis for those who wish. Furthermore, understanding the genetic cause(s) of nemaline myopathy will increase our understanding of muscle biology and provide insights into future development of specific treatments and therapies.

Genetics

Nemaline myopathy may be passed on from parents to children in some families, while in others, it may arise for the first time, with no previous family history of the disorder. When a genetic change occurs for the first time in an individual, it is known as sporadic. On the other hand, when NM is inherited, it can be passed on in an autosomal dominant or in an autosomal recessive form.
Microscopic structures called thin filaments, are in part responsible for the formation of skeletal muscle fibers. The thin filaments are in turn formed by different kinds of muscle-specific proteins, many of which are altered in NM. Currently, we know of five proteins that when altered, can cause NM. These proteins are called actin, tropomyosin 2, tropomyosin 3, troponin T, and nebulin. The figure shown below illustrates how these proteins get together to form the skeletal muscle thin filaments:

All proteins are made by genes. Genes are individual units of information that tell the body all the necessary instructions for development and function. The DNA, also known as the genetic material, is the chemical structure that harbors all of our genes. Sometimes genes acquire mutations. Mutations are DNA changes that have an impact on our health. As the figure above shows, the genes that make actin, tropomyosin 2, tropomyosin 3, troponin T, and nebulin are called:

ACTA1
TPM2
TPM3
NEB
TNNT1

Recently we discovered mututation in a sixth gene for NM called CFL2.
A person with NM may have an alteration in one of these five genes, resulting in a protein that does not work properly. Some patients that have been diagnosed with NM, when tested, have no detectable alteration in any of the known genes. This why it is suspected that there may be additional genes involved in the cause of this condition that have not been discovered yet.
Although there is no clinical diagnostic genetic testing for TPM2, TPM3, NEB or TNNT1, GeneDx offers clinical testing for ACTA1 mutations. As you read above, ACTA1 mutations are responsible for approximately 15 % (15 in 100) cases of NM. This means that a negative ACTA1 test does not rule out the possibility of passing NM to a child.

Research

In the Beggs Laboratory, one of our goals is to determine which additional genes and proteins are involved in nemaline myopathy. If you are the parent of a child with nemaline myopathy, if you yourself are affected, or if you are the healthcare provider of a patient with nemaline myopathy, you may be able to help us find new genes and proteins associated with nemaline myopathy. With the generous help of enough candidate families, we may be able to learn information that will hopefully help us to better understand this disorder, improve diagnosis and develop new treatments and therapeutic methods.

Non-Specific Congenital Myopathies - Undef CM

The congenital myopathies are rare disorders that result in muscle weakness of variable severity. Some patients are affected from birth, while others may develop symptoms in childhood or adulthood. Although patients with some types may not survive past the first few years of life, others may walk independently through adulthood and have families of their own.
The diagnosis of congenital myopathies is usually made from a muscle biopsy. Sometimes, specific muscle changes such as rods or tubules are found in these biopsies. However, on occasions, the muscle biopsy of a patient with a congenital myopathy does not reveal specific changes that would help to establish a diagnosis. Our laboratory is interested in studying DNA and muscle biopsy samples of these patients since it would provide insight into the genetic cause of their muscular condition.
Identification of these genes could have direct clinical benefit to patients and their families by allowing for specific diagnostic testing such as carrier detection and prenatal diagnosis for those who wish. Furthermore, understanding the genetic cause (s) of congenital myopathies will increase our understanding of muscle biology and provide insights into future development of specific treatments and therapies.

Genetics

Most congenital myopathies are thought to have a genetic cause. This means that the condition is caused by alterations in certain genes that are involved in muscle function and/or development. Despite this, most often, congenital myopathies happen in families where there is no previous history of neuromuscular disorders. In these cases, we say that the genetic condition occurred sporadically. Although genetic changes can arise sporadically, once the change appears in a person's genes, the alteration can be passed on from an affected parent to children in a specific pattern of inheritance. Inheritance patterns may vary among different families. It is the purpose of our study to understand these alterations, how they can arise and how they are inherited.

Research

One of the goals of the research done at the Beggs laboratory is to determine which genes and proteins are involved in the cause of congenital myopathies with non-specific muscle changes. We hope that what we learn will be useful for improving diagnosis and treatment of these conditions. If you are the parent of a child with a congenital myopathy, if you yourself are affected, or if you are the healthcare provider of a patient with this condition, you may be able to help us to better understand neuromuscular conditions, and to develop better tests, therapies and treatments.

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Patient and Family Support

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Some families have told us how challenging it was to absorb and process all the information they received during the initial diagnosis of their child. Individuals that were diagnosed during adulthood have also commented about how hard it has been to adjust to the news. Other families have contacted us asking about clinics, support groups, meetings, and programs.

As part of their follow up services, the Muscular Dystrophy Association(MDA) has healthcare service coordinators, professionals who are trained to provide information and support to families with neuromuscular disease. Healthcare Service Coordinators are ready to assist families during their visit to the MDA clinic, helping to obtain equipment and services, providing information about activities, meetings and programs, as well as giving referrals to other services. You can locate the Healthcare Service Coordinators in your area by visiting the MDA website.

In the Greater Boston area, there are two MDA offices. Although these offices are located in the Greater Boston area, their representatives can put you in contact with the MDA office in your area.

Participating in Research

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Many families have contacted us to express their interest in supporting the research on the congenital myopathies by participating in a study. While families should not expect that participation will have any direct impact on their medical care, they can be confident that their help is crucial to moving forward towards a better understanding of these diseases and eventual development of improved tests and treatments. In the event that we make any clinically relevant discoveries about a particular participant, that person may choose to be notified through their physician of the availability of a clinical test. We can then help arrange for this testing to be done by a CLIA-certified clinical diagnostic laboratory.

For some families, results from these studies have opened the possibility for genetic counseling, carrier testing and prenatal diagnosis. These families have used this information to make informed decisions about family planning and other events in the future. Some participant families opt not to find out their genetic status. They just want to contribute to research, hoping that their participation will benefit others along the way. The congenital myopathies are generally not well understood. In the Beggs lab, we know we must start somewhere. To reach our goals, we count on volunteer families to enroll in our studies. If you are the parent of an affected child, or if you yourself are affected, you can make an important difference by helping us to learn more about the congenital myopathies.

Families who participate take four steps:

1) Informed Consent
All participants carefully read and sign informed consent forms authorizing our lab to perform studies on their samples. Each participant family member needs to sign a consent form. A parent/guardian should provide consent if the participant is less than 18 years old.

2) Authorization for Release of Medical Information
We will ask written permission to obtain medical records that are relevant to the diagnosis in the family. This is done as part of the informed consent or by asking the patient (or a parent/guardian if the patient is less than 18 years old) to sign a medical release form. We may also ask some questions about the family's medical history. This can be done through a brief telephone interview. In the event that we find a genetic change in the family, medical information will enable us to compare genetic data with existing clinical data.

3) Blood Sample
We ask for a blood sample from all available and consenting family members. We need approximately three teaspoons for adults and at least one for children less than 3 years old. The blood sample will be used to isolate the genetic material (DNA). The DNA will be screened for alterations in genes that may cause the neuromuscular disease in the family. We can arrange the blood draw through a participant's physician or a nearby medical facility. All costs for the blood draw are paid by our laboratory.

4) Muscle Tissue from an Existing Biopsy
We would like to study a small piece of muscle tissue from you or your child in order to gain a better understanding of the neuromuscular condition in your family. This may be tissue remaining from a previous muscle biopsy, autopsy, or other medically indicated procedure. We will not ask you to have a biopsy solely for the purpose of research. If your tissue sample is stored at another hospital, we will ask your permission to have it shipped to us.

Why are muscle samples important?

Patients often ask why muscle samples are so important for our research. Some have expressed a concern about what we will specifically do with their tissue. The answer is simple. Because the congenital myopathies affect muscle tissue, a close look into the muscle of an affected patient is absolutely essential to give us a more clear understanding of their disorder. Here are a few examples of what we can do with a muscle tissue sample:

Muscle tissue samples are used in microarray studies. Microarrays allow us to analyze theRNA, an important intermediary in the process of making proteins from DNA. Differences in RNA expression may suggest a mutation that would be missed if studying DNA only.

We know of patients who do not have a mutation in any of the neuromuscular disease-causing genes we know about. For this reason, we suspect that there are additional genes yet to be discovered. Looking into the muscle itself can provide insights into this.

The study of a muscle tissue sample gives us the opportunity to analyze the gene "networks" and learn about the process that leads to muscle disease.

In some cases we will use the tissue to purify muscle cells, which we can grow in the lab and use as a model of your condition.

If fresh (unfrozen) tissue is available, we may use the specimen to isolate cells for the purpose of researching possible treatments for neuromuscular disorders.

Cost and Time Commitment:

Participation is free of charge and travel to Boston is not required. The telephone interview, blood draw, and paperwork should take no more than 2 hours to complete.

Reporting of Results:

Because our laboratory is a research laboratory, we cannot release individual results directly to patients. This is because in the United States, the Clinical Laboratory Improvement Act/Amendment (CLIA) only provides authorization to clinical laboratories to do so. However, if we do obtain information that might be significant to the family, we can have these results confirmed and reported by a CLIA-certified clinical laboratory. Although participation in research is free of cost, there is usually a charge associated with confirming results through a clinical lab. The clinical laboratory fees, nevertheless, are usually covered by most health insurance policies.

Study Duration:

Our work consists of studies of indefinite duration. Therefore, it is impossible for us to predict when, if ever, we may have results. Often, studies may take several years or more to complete. Regardless, the participation of patients and their families is a generous contribution toward our understanding of the congenital myopathies. Participants and/or their physicians are welcome to contact us anytime for an update on the research.

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